A Blog Around The Clock

Friday – PLoS Genetics, Pathogens, Computational Biology and ONE published today. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Mendeley, Connotea, Stumbleupon, Facebook and Digg) with just one click. Here are my own picks for the week – you go and look for your own favourites:
Circadian KaiC Phosphorylation: A Multi-Layer Network:

Circadian clocks are endogenous timing mechanisms that allow living organisms to coordinate their activities with daily environmental fluctuations. In cyanobacteria, almost all the genes are rhythmically expressed with the same ~24 h period yet exhibit a variety of phase relationships and waveforms. Remarkably, the core pacemaker ticks robustly via simple biochemical reactions carried out by three Kai proteins: KaiC undergoes circadian phosphorylation in the presence of KaiA, KaiB and ATP. In this work, we propose a reaction network modeling the Kai oscillator based on the differentiation of dual phosphorylation sites. We found a dynamic diversity in KaiC phosphorylation which may serve as a potential regulatory mechanism related to the diverse-phased genome-wide expressions in cyanobacteria. In addition, we deduce that each KaiC hexamer is a single oscillator in regulating its own phosphorylation and interactions with KaiA or/and KaiB. In complex organisms, a number of key clock components possess similar activities (e.g., phosphorylation) with multiple nonequivalent active sites, and they may also show some unusual dynamic features that are embedded in the proteins’ own reaction networks. We hope our work could be helpful to study the correlations between gene expressions and circadian rhythm in prokaryotic cells, even in eukaryotic cells.

Evaluation of the Oscillatory Interference Model of Grid Cell Firing through Analysis and Measured Period Variance of Some Biological Oscillators:

For many animals, including rats, accurate spatial memory over relatively large areas is important in order to find food and shelter. Just as unique points in time can be efficiently represented by combinations of repeating elements like hours, days, and months, points in space can be represented as combinations of elements that repeat at different spatial scales. Just such a code has been identified in the brains of rats and it shows an intriguing triangular spacing of encoded locations. Two different explanations have been developed as to what general mechanism in the brain might be able to generate this unusual code. However, to date there is not conclusive experimental evidence indicating whether either of the two explanations is correct. Here we show in detail that one of the explanations, called oscillatory interference, has specific requirements regarding the amount of variability in the system that implements it. We then report data experimentally examining candidate systems to evaluate their levels of noise. The large amount of noise that we find presents a challenge to the currently suggested biological implementations of oscillatory interference, but it does not provide support for the alternative explanation.

10 Reasons to be Tantalized by the B73 Maize Genome:

Why should you read about the maize genome? Now that so many eukaryotic genomes are available, it’s easy to be blasé… just another few billion bases, grist for constructing gene trees. Why is this new information, so recently shared, worth considering? I am convinced, as I propose you will be too as you read on, that both geneticists and genome consumers will benefit from the first description of the B73 maize genome [1] and equally so from the companion papers compiled in this special collection (http://collections.plos.org/plosgenetics​/maize.php ).

On Theoretical Models of Gene Expression Evolution with Random Genetic Drift and Natural Selection:

The relative contributions of natural selection and random genetic drift are a major source of debate in the study of gene expression evolution, which is hypothesized to serve as a bridge from molecular to phenotypic evolution. It has been suggested that the conflict between views is caused by the lack of a definite model of the neutral hypothesis, which can describe the long-run behavior of evolutionary change in mRNA abundance. Therefore previous studies have used inadequate analogies with the neutral prediction of other phenomena, such as amino acid or nucleotide sequence evolution, as the null hypothesis of their statistical inference. In this study, we introduced two novel theoretical models, one based on neutral drift and the other assuming natural selection, by focusing on a common property of the distribution of mRNA abundance among a variety of eukaryotic cells, which reflects the result of long-term evolution. Our results demonstrated that (1) our models can reproduce two independently found phenomena simultaneously: the time development of gene expression divergence and Zipf’s law of the transcriptome; (2) cytological constraints can be explicitly formulated to describe long-term evolution; (3) the model assuming that natural selection optimized relative mRNA abundance was more consistent with previously published observations than the model of optimized absolute mRNA abundances. The models introduced in this study give a formulation of evolutionary change in the mRNA abundance of each gene as a stochastic process, on the basis of previously published observations. This model provides a foundation for interpreting observed data in studies of gene expression evolution, including identifying an adequate time scale for discriminating the effect of natural selection from that of random genetic drift of selectively neutral variations.

Combination of Real-Value Smell and Metaphor Expression Aids Yeast Detection:

Smell provides important information about the quality of food and drink. Most well-known for their expertise in wine tasting, sommeliers sniff out the aroma of wine and describe them using beautiful metaphors. In contrast, electronic noses, devices that mimic our olfactory recognition system, also detect smells using their sensors but describe them using electronic signals. These devices have been used to judge the freshness of food or detect the presence of pathogenic microorganisms. However, unlike information from gas chromatography, it is difficult to compare odour information collected by these devices because they are made for smelling specific smells and their data are relative intensities. Here, we demonstrate the use of an absolute-value description method using known smell metaphors, and early detection of yeast using the method. This technique may help distinguishing microbial-contamination of food products earlier, or improvement of the food-product qualities.

Motor and Linguistic Linking of Space and Time in the Cerebellum:

Recent literature documented the presence of spatial-temporal interactions in the human brain. The aim of the present study was to verify whether representation of past and future is also mapped onto spatial representations and whether the cerebellum may be a neural substrate for linking space and time in the linguistic domain. We asked whether processing of the tense of a verb is influenced by the space where response takes place and by the semantics of the verb. Responses to past tense were facilitated in the left space while responses to future tense were facilitated in the right space. Repetitive transcranial magnetic stimulation (rTMS) of the right cerebellum selectively slowed down responses to future tense of action verbs; rTMS of both cerebellar hemispheres decreased accuracy of responses to past tense in the left space and to future tense in the right space for non-verbs, and to future tense in the right space for state verbs. The results suggest that representation of past and future is mapped onto spatial formats and that motor action could represent the link between spatial and temporal dimensions. Right cerebellar, left motor brain networks could be part of the prospective brain, whose primary function is to use past experiences to anticipate future events. Both cerebellar hemispheres could play a role in establishing the grammatical rules for verb conjugation.

Genome-Wide Scan for Signatures of Human Population Differentiation and Their Relationship with Natural Selection, Functional Pathways and Diseases:

Genetic differences both between individuals and populations are studied for their evolutionary relevance and for their potential medical applications. Most of the genetic differentiation among populations are caused by random drift that should affect all loci across the genome in a similar manner. When a locus shows extraordinary high or low levels of population differentiation, this may be interpreted as evidence for natural selection. The most used measure of population differentiation was devised by Wright and is known as fixation index, or FST. We performed a genome-wide estimation of FST on about 4 millions of SNPs from HapMap project data. We demonstrated a heterogeneous distribution of FST values between autosomes and heterochromosomes. When we compared the FST values obtained in this study with another evolutionary measure obtained by comparative interspecific approach, we found that genes under positive selection appeared to show low levels of population differentiation. We applied a gene set approach, widely used for microarray data analysis, to detect functional pathways under selection. We found that one pathway related to antigen processing and presentation showed low levels of FST, while several pathways related to cell signalling, growth and morphogenesis showed high FST values. Finally, we detected a signature of selection within genes associated with human complex diseases. These results can help to identify which process occurred during human evolution and adaptation to different environments. They also support the hypothesis that common diseases could have a genetic background shaped by human evolution.

A Mechanistic Niche Model for Measuring Species’ Distributional Responses to Seasonal Temperature Gradients:

Niche theory is central to understanding how species respond geographically to climate change. It defines a species’ realized niche in a biological community, its fundamental niche as determined by physiology, and its potential niche–the fundamental niche in a given environment or geographic space. However, most predictions of the effects of climate change on species’ distributions are limited to correlative models of the realized niche, which assume that species are in distributional equilibrium with respect to the variables or gradients included in the model. Here, I present a mechanistic niche model that measures species’ responses to major seasonal temperature gradients that interact with the physiology of the organism. I then use lethal physiological temperatures to parameterize the model for bird species in North and South America and show that most focal bird species are not in direct physiological equilibrium with the gradients. Results also show that most focal bird species possess broad thermal tolerances encompassing novel climates that could become available with climate change. I conclude with discussion of how mechanistic niche models may be used to (i) gain insights into the processes that cause species to respond to climate change and (ii) build more accurate correlative distribution models in birds and other species.

There are 25 new articles in PLoS ONE today. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Mendeley, Connotea, Stumbleupon, Facebook and Digg) with just one click. Here are my own picks for the week – you go and look for your own favourites:
The Astronomical Orientation of Ancient Greek Temples:

Despite its appearing to be a simple question to answer, there has been no consensus as to whether or not the alignments of ancient Greek temples reflect astronomical intentions. Here I present the results of a survey of archaic and classical Greek temples in Sicily and compare them with temples in Greece. Using a binomial test I show strong evidence that there is a preference for solar orientations. I then speculate that differences in alignment patterns between Sicily and Greece reflect differing pressures in the expression of ethnic identity.

Distributed Network, Wireless and Cloud Computing Enabled 3-D Ultrasound; a New Medical Technology Paradigm:

Medical technologies are indispensable to modern medicine. However, they have become exceedingly expensive and complex and are not available to the economically disadvantaged majority of the world population in underdeveloped as well as developed parts of the world. For example, according to the World Health Organization about two thirds of the world population does not have access to medical imaging. In this paper we introduce a new medical technology paradigm centered on wireless technology and cloud computing that was designed to overcome the problems of increasing health technology costs. We demonstrate the value of the concept with an example; the design of a wireless, distributed network and central (cloud) computing enabled three-dimensional (3-D) ultrasound system. Specifically, we demonstrate the feasibility of producing a 3-D high end ultrasound scan at a central computing facility using the raw data acquired at the remote patient site with an inexpensive low end ultrasound transducer designed for 2-D, through a mobile device and wireless connection link between them. Producing high-end 3D ultrasound images with simple low-end transducers reduces the cost of imaging by orders of magnitude. It also removes the requirement of having a highly trained imaging expert at the patient site, since the need for hand-eye coordination and the ability to reconstruct a 3-D mental image from 2-D scans, which is a necessity for high quality ultrasound imaging, is eliminated. This could enable relatively untrained medical workers in developing nations to administer imaging and a more accurate diagnosis, effectively saving the lives of people.

Generation and Characterization of Fmr1 Knockout Zebrafish:

Fragile X syndrome (FXS) is one of the most common known causes of inherited mental retardation. The gene mutated in FXS is named FMR1, and is well conserved from human to Drosophila. In order to generate a genetic tool to study FMR1 function during vertebrate development, we generated two mutant alleles of the fmr1 gene in zebrafish. Both alleles produce no detectable Fmr protein, and produce viable and fertile progeny with lack of obvious phenotypic features. This is in sharp contrast to published results based on morpholino mediated knock-down of fmr1, reporting defects in craniofacial development and neuronal branching in embryos. These phenotypes we specifically addressed in our knock-out animals, revealing no significant deviations from wild-type animals, suggesting that the published morpholino based fmr1 phenotypes are potential experimental artifacts. Therefore, their relation to fmr1 biology is questionable and morpholino induced fmr1 phenotypes should be avoided in screens for potential drugs suitable for the treatment of FXS. Importantly, a true genetic zebrafish model is now available which can be used to study FXS and to derive potential drugs for FXS treatment.

Emotional Modulation of Attention: Fear Increases but Disgust Reduces the Attentional Blink:

It is well known that facial expressions represent important social cues. In humans expressing facial emotion, fear may be configured to maximize sensory exposure (e.g., increases visual input) whereas disgust can reduce sensory exposure (e.g., decreases visual input). To investigate whether such effects also extend to the attentional system, we used the “attentional blink” (AB) paradigm. Many studies have documented that the second target (T2) of a pair is typically missed when presented within a time window of about 200-500 ms from the first to-be-detected target (T1; i.e., the AB effect). It has recently been proposed that the AB effect depends on the efficiency of a gating system which facilitates the entrance of relevant input into working memory, while inhibiting irrelevant input. Following the inhibitory response on post T1 distractors, prolonged inhibition of the subsequent T2 is observed. In the present study, we hypothesized that processing facial expressions of emotion would influence this attentional gating. Fearful faces would increase but disgust faces would decrease inhibition of the second target. We showed that processing fearful versus disgust faces has different effects on these attentional processes. We found that processing fear faces impaired the detection of T2 to a greater extent than did the processing disgust faces. This finding implies emotion-specific modulation of attention. Based on the recent literature on attention, our finding suggests that processing fear-related stimuli exerts greater inhibitory responses on distractors relative to processing disgust-related stimuli. This finding is of particular interest for researchers examining the influence of emotional processing on attention and memory in both clinical and normal populations. For example, future research could extend upon the current study to examine whether inhibitory processes invoked by fear-related stimuli may be the mechanism underlying the enhanced learning of fear-related stimuli.

Synergy between Repellents and Organophosphates on Bed Nets: Efficacy and Behavioural Response of Natural Free-Flying An. gambiae Mosquitoes:

Chemicals are used on bed nets in order to prevent infected bites and to kill aggressive malaria vectors. Because pyrethroid resistance has become widespread in the main malaria vectors, research for alternative active ingredients becomes urgent. Mixing a repellent and a non-pyrethroid insecticide seemed to be a promising tool as mixtures in the laboratory showed the same features as pyrethroids. We present here the results of two trials run against free-flying Anopheles gambiae populations comparing the effects of two insect repellents (either DEET or KBR 3023, also known as icaridin) and an organophosphate insecticide at low-doses (pirimiphos-methyl, PM) used alone and in combination on bed nets. We showed that mixtures of PM and the repellents induced higher exophily, blood feeding inhibition and mortality among wild susceptible and resistant malaria vectors than compounds used alone. Nevertheless the synergistic interactions are only involved in the high mortality induced by the two mixtures. These field trials argue in favour of the strategy of mixing repellent and organophosphate on bed nets to better control resistant malaria vectors.

Survival and Cardioprotective Benefits of Long-Term Blueberry Enriched Diet in Dilated Cardiomyopathy Following Myocardial Infarction in Rats:

Despite remarkable progress in treatment of chronic heart failure (CHF) over the last two decades, mortality, personal suffering and cost remain staggering, and effective interventions are still a challenge. Previously we reported that a blueberry-enriched diet (BD) attenuated necroapoptosis and inflammation in periinfarct area in a rat model of myocardial infarction (MI). To test the hypothesis that BD will attenuate the course of CHF, including mortality and cardiac remodeling during the first year after induction of MI in rats. Two weeks after coronary artery ligation, rats were divided into two groups of similar average MI size, measured by echocardiography, and then12-mo dietary regimens were initiated as follows: ad libitum regular diet (control, CD, n = 27) and isocaloric food with 2% blueberry supplement (BD, n = 27) also available ad libitum. These dietary groups were compared to each other and to sham group (SH). Mortality over the 12 mo was reduced by 22% in BD compared with CD (p<0.01). In the course of developing CHF, BD had no effect on the body weight, heart rate or blood pressure. Bi-monthly Echo revealed significant attenuation of the LV chamber remodeling, LV posterior wall thinning, and MI expansion in BD compared with CD. In fact, BD arrested the MI expansion. This is the first experimental evidence that a blueberry-enriched diet has positive effects on the course of CHF and thus warrants consideration for clinical evaluation.

There are 28 new articles in PLoS ONE today. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Mendeley, Connotea, Stumbleupon, Facebook and Digg) with just one click. Here are my own picks for the week – you go and look for your own favourites:
Breaking the News or Fueling the Epidemic? Temporal Association between News Media Report Volume and Opioid-Related Mortality:

Historical studies of news media have suggested an association between reporting and increased drug abuse. Period effects for substance use have been documented for different classes of legal and illicit substances, with the suspicion that media publicity may have played major roles in their emergence. Previous analyses have drawn primarily from qualitative evidence; the temporal relationship between media reporting volume and adverse health consequences has not been quantified nationally. We set out to explore whether we could find a quantitative relationship between media reports about prescription opioid abuse and overdose mortality associated with these drugs. We assessed whether increases in news media reports occurred before or after increases in overdose deaths. Our ecological study compared a monthly time series of unintentional poisoning deaths involving short-acting prescription opioid substances, from 1999 to 2005 using multiple cause-of-death data published by the National Center for Health Statistics, to monthly counts of English-language news articles mentioning generic and branded names of prescription opioids obtained from Google News Archives from 1999 to 2005. We estimated the association between media volume and mortality rates by time-lagged regression analyses. There were 24,272 articles and 30,916 deaths involving prescription opioids during the seven-year study period. Nationally, the number of articles mentioning prescription opioids increased dramatically starting in early 2001, following prominent coverage about the nonmedical use of OxyContin. We found a significant association between news reports and deaths, with media reporting preceding fatal opioid poisonings by two to six months and explaining 88% (p<0.0001, df 78) of the variation in mortality. While availability, structural, and individual predispositions are key factors influencing substance use, news reporting may enhance the popularity of psychoactive substances. Albeit ecological in nature, our finding suggests the need for further evaluation of the influence of news media on health. Reporting on prescription opioids conforms to historical patterns of news reporting on other psychoactive substances.

Rhesus Monkeys’ Valuation of Vocalizations during a Free-Choice Task:

Adaptive behavior requires that animals integrate current and past information with their decision-making. One important type of information is auditory-communication signals (i.e., species-specific vocalizations). Here, we tested how rhesus monkeys incorporate the opportunity to listen to different species-specific vocalizations into their decision-making processes. In particular, we tested how monkeys value these vocalizations relative to the opportunity to get a juice reward. To test this hypothesis, monkeys chose one of two targets to get a varying juice reward; at one of those targets, in addition to the juice reward, a vocalization was presented. By titrating the juice amounts at the two targets, we quantified the relationship between the monkeys’ juice choices relative to the opportunity to listen to a vocalization. We found that, rhesus were not willing to give up a large juice reward to listen to vocalizations indicating that, relative to a juice reward, listening to vocalizations has a low value.

The Typical Flight Performance of Blowflies: Measuring the Normal Performance Envelope of Calliphora vicina Using a Novel Corner-Cube Arena:

Despite a wealth of evidence demonstrating extraordinary maximal performance, little is known about the routine flight performance of insects. We present a set of techniques for benchmarking performance characteristics of insects in free flight, demonstrated using a model species, and comment on the significance of the performance observed. Free-flying blowflies (Calliphora vicina) were filmed inside a novel mirrored arena comprising a large (1.6 m1.6 m1.6 m) corner-cube reflector using a single high-speed digital video camera (250 or 500 fps). This arrangement permitted accurate reconstruction of the flies’ 3-dimensional trajectories without the need for synchronisation hardware, by virtue of the multiple reflections of a subject within the arena. Image sequences were analysed using custom-written automated tracking software, and processed using a self-calibrating bundle adjustment procedure to determine the subject’s instantaneous 3-dimensional position. We illustrate our method by using these trajectory data to benchmark the routine flight performance envelope of our flies. Flight speeds were most commonly observed between 1.2 ms−1 and 2.3 ms−1, with a maximum of 2.5 ms−1. Our flies tended to dive faster than they climbed, with a maximum descent rate (−2.4 ms−1) almost double the maximum climb rate (1.2 ms−1). Modal turn rate was around 240°s−1, with maximal rates in excess of 1700°s−1. We used the maximal flight performance we observed during normal flight to construct notional physical limits on the blowfly flight envelope, and used the distribution of observations within that notional envelope to postulate behavioural preferences or physiological and anatomical constraints. The flight trajectories we recorded were never steady: rather they were constantly accelerating or decelerating, with maximum tangential accelerations and maximum centripetal accelerations on the order of 3 g.

In-Group Conformity Sustains Different Foraging Traditions in Capuchin Monkeys (Cebus apella):

Decades of research have revealed rich cultural repertoires encompassing multiple traditions in wild great apes, a picture crucially complemented by experimental simulations with captive apes. Studies with wild capuchin monkeys, the most encephalized simian species, have indicated a New World convergence on these cultural phenomena, involving multiple traditions and tool use. However, experimental studies to date are in conflict with such findings in concluding that capuchins, like other monkeys, show minimal capacities for social learning. Here we report a new experimental approach in which the alpha male of each of two groups of capuchins was trained to open an artificial foraging device in a quite different way, using either a slide or lift action, then reunited with his group. In each group a majority of monkeys, 8 of 11 and 13 of 14, subsequently mastered the task. Seventeen of the successful 21 monkeys discovered the alternative action to that seeded in the group, performing it a median of 4 times. Nevertheless, all 21 primarily adopted the technique seeded by their group’s alpha male. Median proportions of slide versus lift were 0.96 for the group seeded with slide versus 0. 01 for the group seeded with lift. These results suggest a striking effect of social conformity in learned behavioral techniques, consistent with field reports of capuchin traditions and convergent on the only other species in which such cultural phenomena have been reported, chimpanzees and humans.

The Real maccoyii: Identifying Tuna Sushi with DNA Barcodes – Contrasting Characteristic Attributes and Genetic Distances:

The use of DNA barcodes for the identification of described species is one of the least controversial and most promising applications of barcoding. There is no consensus, however, as to what constitutes an appropriate identification standard and most barcoding efforts simply attempt to pair a query sequence with reference sequences and deem identification successful if it falls within the bounds of some pre-established cutoffs using genetic distance. Since the Renaissance, however, most biological classification schemes have relied on the use of diagnostic characters to identify and place species. Here we developed a cytochrome c oxidase subunit I character-based key for the identification of all tuna species of the genus Thunnus, and compared its performance with distance-based measures for identification of 68 samples of tuna sushi purchased from 31 restaurants in Manhattan (New York City) and Denver, Colorado. Both the character-based key and GenBank BLAST successfully identified 100% of the tuna samples, while the Barcode of Life Database (BOLD) as well as genetic distance thresholds, and neighbor-joining phylogenetic tree building performed poorly in terms of species identification. A piece of tuna sushi has the potential to be an endangered species, a fraud, or a health hazard. All three of these cases were uncovered in this study. Nineteen restaurant establishments were unable to clarify or misrepresented what species they sold. Five out of nine samples sold as a variant of “white tuna” were not albacore (T. alalunga), but escolar (Lepidocybium flavorunneum), a gempylid species banned for sale in Italy and Japan due to health concerns. Nineteen samples were northern bluefin tuna (T. thynnus) or the critically endangered southern bluefin tuna (T. maccoyii), though nine restaurants that sold these species did not state these species on their menus. The Convention on International Trade Endangered Species (CITES) requires that listed species must be identifiable in trade. This research fulfills this requirement for tuna, and supports the nomination of northern bluefin tuna for CITES listing in 2010.

Nestedness of Ectoparasite-Vertebrate Host Networks:

Determining the structure of ectoparasite-host networks will enable disease ecologists to better understand and predict the spread of vector-borne diseases. If these networks have consistent properties, then studying the structure of well-understood networks could lead to extrapolation of these properties to others, including those that support emerging pathogens. Borrowing a quantitative measure of network structure from studies of mutualistic relationships between plants and their pollinators, we analyzed 29 ectoparasite-vertebrate host networks–including three derived from molecular bloodmeal analysis of mosquito feeding patterns–using measures of nestedness to identify non-random interactions among species. We found significant nestedness in ectoparasite-vertebrate host lists for habitats ranging from tropical rainforests to polar environments. These networks showed non-random patterns of nesting, and did not differ significantly from published estimates of nestedness from mutualistic networks. Mutualistic and antagonistic networks appear to be organized similarly, with generalized ectoparasites interacting with hosts that attract many ectoparasites and more specialized ectoparasites usually interacting with these same “generalized” hosts. This finding has implications for understanding the network dynamics of vector-born pathogens. We suggest that nestedness (rather than random ectoparasite-host associations) can allow rapid transfer of pathogens throughout a network, and expand upon such concepts as the dilution effect, bridge vectors, and host switching in the context of nested ectoparasite-vertebrate host networks.

Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium:

The emergence in 2009 of a swine-origin H1N1 influenza virus as the first pandemic of the 21st Century is a timely reminder of the international public health impact of influenza viruses, even those associated with mild disease. The widespread distribution of highly pathogenic H5N1 influenza virus in the avian population has spawned concern that it may give rise to a human influenza pandemic. The mortality rate associated with occasional human infection by H5N1 virus approximates 60%, suggesting that an H5N1 pandemic would be devastating to global health and economy. To date, the H5N1 virus has not acquired the propensity to transmit efficiently between humans. The reasons behind this are unclear, especially given the high mutation rate associated with influenza virus replication. Here we used a panel of recombinant H5 hemagglutinin (HA) variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for influenza virus infection and spread. While parental H5 HA exhibited limited binding to human tracheal epithelium, introduction of selected mutations converted the binding profile to that of a current human influenza strain HA. Strikingly, these amino-acid changes required multiple simultaneous mutations in the genomes of naturally occurring H5 isolates. Moreover, H5 HAs bearing intermediate sequences failed to bind airway tissues and likely represent mutations that are an evolutionary “dead end.” We conclude that, although genetic changes that adapt H5 to human airways can be demonstrated, they may not readily arise during natural virus replication. This genetic barrier limits the likelihood that current H5 viruses will originate a human pandemic.

Genetic Variation and Recent Positive Selection in Worldwide Human Populations: Evidence from Nearly 1 Million SNPs:

Genome-wide scans of hundreds of thousands of single-nucleotide polymorphisms (SNPs) have resulted in the identification of new susceptibility variants to common diseases and are providing new insights into the genetic structure and relationships of human populations. Moreover, genome-wide data can be used to search for signals of recent positive selection, thereby providing new insights into the genetic adaptations that occurred as modern humans spread out of Africa and around the world. We genotyped approximately 500,000 SNPs in 255 individuals (5 individuals from each of 51 worldwide populations) from the Human Genome Diversity Panel (HGDP-CEPH). When merged with non-overlapping SNPs typed previously in 250 of these same individuals, the resulting data consist of over 950,000 SNPs. We then analyzed the genetic relationships and ancestry of individuals without assigning them to populations, and we also identified candidate regions of recent positive selection at both the population and regional (continental) level. Our analyses both confirm and extend previous studies; in particular, we highlight the impact of various dispersals, and the role of substructure in Africa, on human genetic diversity. We also identified several novel candidate regions for recent positive selection, and a gene ontology (GO) analysis identified several GO groups that were significantly enriched for such candidate genes, including immunity and defense related genes, sensory perception genes, membrane proteins, signal receptors, lipid binding/metabolism genes, and genes involved in the nervous system. Among the novel candidate genes identified are two genes involved in the thyroid hormone pathway that show signals of selection in African Pygmies that may be related to their short stature.

Extrapair Paternity and Maternity in the Three-Toed Woodpecker, Picoides tridactylus: Insights from Microsatellite-Based Parentage Analysis:

Molecular techniques have revealed that avian mating systems are more diverse and complex than previously thought. We used microsatellite markers to determine genetic parentage, the prevalence of extrapair paternity and quasi-parasitism (i.e. situations where a male’s extrapair mate lay in his nest) in a socially monogamous population of three-toed woodpeckers (Picoides tridactylus) in southern Finland. A total of 129 adults and nestlings, representing 5-9 families annually from 2004-2007, were genotyped at up to ten microsatellite loci. The results of genetic assignment tests confirmed that monogamous parentage characterized the majority (84.6%, 22/26) of broods, and that most (93.8%, 75/80) nestlings were the offspring of their social parents. Two of 80 nestlings (2.5%) in two of 26 broods (7.7%) were sired by extrapair males and quasi-parasitism occurred in 3.8% (3/80) of nestlings and 7.7% (2/26) of broods. Hence, the levels of extrapair parentage were low, possibly because both genetic polygyny and polyandry are constrained by the high paternal effort required for parental care. The co-occurrence of low levels of extrapair paternity and quasi-parasitism are discussed in light of ecological and behavioural factors characterizing the species biology.

Article-Level Metrics and the Evolution of Scientific Impact:

Formally published papers that have been through a traditional prepublication peer review process remain the most important means of communicating science today. Researchers depend on them to learn about the latest advances in their fields and to report their own findings. The intentions of traditional peer review are certainly noble: to ensure methodological integrity and to comment on potential significance of experimental studies through examination by a panel of objective, expert colleagues. In principle, this system enables science to move forward on the collective confidence of previously published work. Unfortunately, the traditional system has inspired methods of measuring impact that are suboptimal for their intended uses.

The Unintended Consequences of Clinical Trials Regulations:

The experience of clinical researchers worldwide indicates that a major obstacle to undertaking academic research is the ever-increasing bureaucracy attached to the process. Recent changes in research governance were intended to ensure that clinical trials are safe and informative. However, the regulatory burden is now obstructing high quality science and has become the biggest single threat to research carried out in academia [1]. We illustrate here this international problem by reference to the regulations imposed by the European Union and the incorporation of these restrictions into UK national law concerning Good Clinical Practice (GCP).

Explaining the Linguistic Diversity of Sahul Using Population Models:

About one-fifth of all the world’s languages are spoken in present day Australia, New Guinea, and the surrounding islands. This corresponds to the boundaries of the ancient continent of Sahul, which broke up due to rising sea levels about 9000 years before present. The distribution of languages in this region conveys information about its population history. The recent migration of the Austronesian speakers can be traced with precision, but the histories of the Papuan and Australian language speakers are considerably more difficult to reconstruct. The speakers of these languages are presumably descendants of the first migrations into Sahul, and their languages have been subject to many millennia of dispersal and contact. Due to the antiquity of these language families, there is insufficient lexical evidence to reconstruct their histories. Instead we use abstract structural features to infer population history, modeling language change as a result of both inheritance and horizontal diffusion. We use a Bayesian phylogenetic clustering method, originally developed for investigating genetic recombination to infer the contribution of different linguistic lineages to the current diversity of languages. The results show the underlying structure of the diversity of these languages, reflecting ancient dispersals, millennia of contact, and probable phylogenetic groups. The analysis identifies 10 ancestral language populations, some of which can be identified with previously known phylogenetic groups (language families or subgroups), and some of which have not previously been proposed.

The Evolution of a Capacity to Build Supra-Cellular Ropes Enabled Filamentous Cyanobacteria to Colonize Highly Erodible Substrates:

Several motile, filamentous cyanobacteria display the ability to self-assemble into tightly woven or twisted groups of filaments that form macroscopic yarns or ropes, and that are often centimeters long and 50-200 µm in diameter. Traditionally, this trait has been the basis for taxonomic definition of several genera, notably Microcoleus and Hydrocoleum, but the trait has not been associated with any plausible function. Through the use of phylogenetic reconstruction, we demonstrate that pedigreed, rope-building cyanobacteria from various habitats do not form a monophyletic group. This is consistent with the hypothesis that rope-building ability was fixed independently in several discrete clades, likely through processes of convergent evolution or lateral transfer. Because rope-building cyanobacteria share the ability to colonize geologically unstable sedimentary substrates, such as subtidal and intertidal marine sediments and non-vegetated soils, it is also likely that this supracellular differentiation capacity imparts a particular fitness advantage in such habitats. The physics of sediment and soil erosion in fact predict that threads in the 50-200 µm size range will attain optimal characteristics to stabilize such substrates on contact. Rope building is a supracellular morphological adaptation in filamentous cyanobacteria that allows them to colonize physically unstable sedimentary environments, and to act as successful pioneers in the biostabilization process.

The Link between Dengue Incidence and El Niño Southern Oscillation:

In a new study by Johansson and colleagues published in this issue of PLoS Medicine [12], the authors carry out statistical time-series analyses to examine the dynamic relationship between climate variables and the incidence of dengue in Thailand, Mexico, and Puerto Rico. They find no systematic association between multi-annual dengue outbreaks and El Niño Southern Oscillation.

Avian Host-Selection by Culex pipiens in Experimental Trials:

Evidence from field studies suggests that Culex pipiens, the primary mosquito vector of West Nile virus (WNV) in the northeastern and north central United States, feeds preferentially on American robins (Turdus migratorius). To determine the contribution of innate preferences to observed preference patterns in the field, we conducted host preference trials with a known number of adult female C. pipiens in outdoor cages comparing the relative attractiveness of American robins with two common sympatric bird species, European starling, Sternus vulgaris and house sparrow, Passer domesticus. Host seeking C. pipiens were three times more likely to enter robin-baited traps when with the alternate host was a European starling (n = 4 trials; OR = 3.06; CI [1.42-6.46]) and almost twice more likely when the alternative was a house sparrow (n = 8 trials; OR = 1.80; CI = [1.22-2.90]). There was no difference in the probability of trap entry when two robins were offered (n = 8 trials). Logistic regression analysis determined that the age, sex and weight of the birds, the date of the trial, starting-time, temperature, humidity, wind-speed and age of the mosquitoes had no effect on the probability of a choosing a robin over an alternate bird. Findings indicate that preferential feeding by C. pipiens mosquitoes on certain avian hosts is likely to be inherent, and we discuss the implications innate host preferences may have on enzootic WNV transmission.

How Can We Support the Use of Systematic Reviews in Policymaking?:

In the last few years the landscape has changed dramatically for policymakers seeking to use research evidence in the policymaking process. The landscape has also changed for the many stakeholders seeking to use research evidence to influence the policymaking process. The task once seemed overwhelming given the dearth of synthesized research evidence on the “big”, typically multifaceted, questions that matter to policymakers and stakeholders [1],[2]. Now it isn’t uncommon for these groups to find dozens of systematic reviews that address the governance, financial, and delivery arrangements within health systems that can determine whether a cost-effective program, service, or drug reaches those who need it. For example, teams of African policymakers, stakeholders, and researchers drew on 30 reviews for what at first glance seems a straightforward question: how to support the widespread use of artemisinin-based combination therapy (ACT) to treat uncomplicated falciparum malaria. The review of qualitative studies of people’s views about and experiences with medicine sellers provided insights that were as central to the process as reviews of the effectiveness of a particular ACT formulation or the home-based management of malaria [3]-[5].

There are 17 new articles published yesterday and 24 new articles today in PLoS ONE. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Mendeley, Connotea, Stumbleupon, Facebook and Digg) with just one click. Here are my own picks for the week – you go and look for your own favourites:
Norwegian Physicians’ Knowledge of and Opinions about Evidence-Based Medicine: Cross-Sectional Study:

Objective
To answer five research questions: Do Norwegian physicians know about the three important aspects of EBM? Do they use EBM methods in their clinical practice? What are their attitudes towards EBM? Has EBM in their opinion changed medical practice during the last 10 years? Do they use EBM based information sources?
Design
Cross sectional survey in 2006.
Setting
Norway.
Participants
966 doctors who responded to a questionnaire (70% response rate).
Results
In total 87% of the physicians mentioned the use of randomised clinical trials as a key aspect of EBM, while 53% of them mentioned use of clinical expertise and only 19% patients’ values. 40% of the respondents reported that their practice had always been evidence-based. Many respondents experienced difficulties in using EBM principles in their clinical practice because of lack of time and difficulties in searching EBM based literature. 80% agreed that EBM helps physicians towards better practice and 52% that it improves patients’ health. As reasons for changes in medical practice 86% of respondents mentioned medical progress, but only 39% EBM.
Conclusions
The results of the study indicate that Norwegian physicians have a limited knowledge of the key aspects of EBM but a positive attitude towards the concept. They had limited experience in the practice of EBM and were rather indifferent to the impact of EBM on medical practice. For solving a patient problem, physicians would rather consult a colleague than searching evidence based resources such as the Cochrane Library.

Campbell’s Monkeys Use Affixation to Alter Call Meaning:

Human language has evolved on a biological substrate with phylogenetic roots deep in the primate lineage. Here, we describe a functional analogy to a common morphological process in human speech, affixation, in the alarm calls of free-ranging adult Campbell’s monkeys (Cercopithecus campbelli campbelli). We found that male alarm calls are composed of an acoustically variable stem, which can be followed by an acoustically invariable suffix. Using long-term observations and predator simulation experiments, we show that suffixation in this species functions to broaden the calls’ meaning by transforming a highly specific eagle alarm to a general arboreal disturbance call or by transforming a highly specific leopard alarm call to a general alert call. We concluded that, when referring to specific external events, non-human primates can generate meaningful acoustic variation during call production that is functionally equivalent to suffixation in human language.

Interference Competition and High Temperatures Reduce the Virulence of Fig Wasps and Stabilize a Fig-Wasp Mutualism:

Fig trees are pollinated by fig wasps, which also oviposit in female flowers. The wasp larvae gall and eat developing seeds. Although fig trees benefit from allowing wasps to oviposit, because the wasp offspring disperse pollen, figs must prevent wasps from ovipositing in all flowers, or seed production would cease, and the mutualism would go extinct. In Ficus racemosa, we find that syconia (‘figs’) that have few foundresses (ovipositing wasps) are underexploited in the summer (few seeds, few galls, many empty ovules) and are overexploited in the winter (few seeds, many galls, few empty ovules). Conversely, syconia with many foundresses produce intermediate numbers of galls and seeds, regardless of season. We use experiments to explain these patterns, and thus, to explain how this mutualism is maintained. In the hot summer, wasps suffer short lifespans and therefore fail to oviposit in many flowers. In contrast, cooler temperatures in the winter permit longer wasp lifespans, which in turn allows most flowers to be exploited by the wasps. However, even in winter, only in syconia that happen to have few foundresses are most flowers turned into galls. In syconia with higher numbers of foundresses, interference competition reduces foundress lifespans, which reduces the proportion of flowers that are galled. We further show that syconia encourage the entry of multiple foundresses by delaying ostiole closure. Taken together, these factors allow fig trees to reduce galling in the wasp-benign winter and boost galling (and pollination) in the wasp-stressing summer. Interference competition has been shown to reduce virulence in pathogenic bacteria. Our results show that interference also maintains cooperation in a classic, cooperative symbiosis, thus linking theories of virulence and mutualism. More generally, our results reveal how frequency-dependent population regulation can occur in the fig-wasp mutualism, and how a host species can ‘set the rules of the game’ to ensure mutualistic behavior in its symbionts.

MVA-Based H5N1 Vaccine Affords Cross-Clade Protection in Mice against Influenza A/H5N1 Viruses at Low Doses and after Single Immunization:

Human infections with highly pathogenic avian influenza viruses of the H5N1 subtype, frequently reported since 2003, result in high morbidity and mortality. It is feared that these viruses become pandemic, therefore the development of safe and effective vaccines is desirable. MVA-based H5N1 vaccines already proved to be effective when two immunizations with high doses were used. Dose-sparing strategies would increase the number of people that can be vaccinated when the amount of vaccine preparations that can be produced is limited. Furthermore, protective immunity is induced ideally after a single immunization. Therefore the minimal requirements for induction of protective immunity with a MVA-based H5N1 vaccine were assessed in mice. To this end, mice were vaccinated once or twice with descending doses of a recombinant MVA expressing the HA gene of influenza virus A/Vietnam/1194/04. The protective efficacy was determined after challenge infection with the homologous clade 1 virus and a heterologous virus derived from clade 2.1, A/Indonesia/5/05 by assessing weight loss, virus replication and histopathological changes. It was concluded that MVA-based vaccines allowed significant dose-sparing and afford cross-clade protection, also after a single immunization, which are favorable properties for an H5N1 vaccine candidate.

There are 23 new articles in PLoS ONE today. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Mendeley, Connotea, Stumbleupon, Facebook and Digg) with just one click. Here are my own picks for the week – you go and look for your own favourites:
Biomechanics of Running Indicates Endothermy in Bipedal Dinosaurs:

One of the great unresolved controversies in paleobiology is whether extinct dinosaurs were endothermic, ectothermic, or some combination thereof, and when endothermy first evolved in the lineage leading to birds. Although it is well established that high, sustained growth rates and, presumably, high activity levels are ancestral for dinosaurs and pterosaurs (clade Ornithodira), other independent lines of evidence for high metabolic rates, locomotor costs, or endothermy are needed. For example, some studies have suggested that, because large dinosaurs may have been homeothermic due to their size alone and could have had heat loss problems, ectothermy would be a more plausible metabolic strategy for such animals. Here we describe two new biomechanical approaches for reconstructing the metabolic rate of 14 extinct bipedal dinosauriforms during walking and running. These methods, well validated for extant animals, indicate that during walking and slow running the metabolic rate of at least the larger extinct dinosaurs exceeded the maximum aerobic capabilities of modern ectotherms, falling instead within the range of modern birds and mammals. Estimated metabolic rates for smaller dinosaurs are more ambiguous, but generally approach or exceed the ectotherm boundary. Our results support the hypothesis that endothermy was widespread in at least larger non-avian dinosaurs. It was plausibly ancestral for all dinosauriforms (perhaps Ornithodira), but this is perhaps more strongly indicated by high growth rates than by locomotor costs. The polarity of the evolution of endothermy indicates that rapid growth, insulation, erect postures, and perhaps aerobic power predated advanced “avian” lung structure and high locomotor costs.

Foreign Subtitles Help but Native-Language Subtitles Harm Foreign Speech Perception:

Understanding foreign speech is difficult, in part because of unusual mappings between sounds and words. It is known that listeners in their native language can use lexical knowledge (about how words ought to sound) to learn how to interpret unusual speech-sounds. We therefore investigated whether subtitles, which provide lexical information, support perceptual learning about foreign speech. Dutch participants, unfamiliar with Scottish and Australian regional accents of English, watched Scottish or Australian English videos with Dutch, English or no subtitles, and then repeated audio fragments of both accents. Repetition of novel fragments was worse after Dutch-subtitle exposure but better after English-subtitle exposure. Native-language subtitles appear to create lexical interference, but foreign-language subtitles assist speech learning by indicating which words (and hence sounds) are being spoken.

Egg Eviction Imposes a Recoverable Cost of Virulence in Chicks of a Brood Parasite:

Chicks of virulent brood parasitic birds eliminate their nestmates and avoid costly competition for foster parental care. Yet, efforts to evict nest contents by the blind and naked common cuckoo Cuculus canorus hatchling are counterintuitive as both adult parasites and large older cuckoo chicks appear to be better suited to tossing the eggs and young of the foster parents. Here we show experimentally that egg tossing imposed a recoverable growth cost of mass gain in common cuckoo chicks during the nestling period in nests of great reed warbler Acrocephalus arundinaceus hosts. Growth rates of skeletal traits and morphological variables involved in the solicitation of foster parental care remained similar between evictor and non-evictor chicks throughout development. We also detected no increase in predation rates for evicting nests, suggesting that egg tossing behavior by common cuckoo hatchlings does not increase the conspicuousness of nests. The temporary growth cost of egg eviction by common cuckoo hatchlings is the result of constraints imposed by rejecter host adults and competitive nestmates on the timing and mechanism of parasite virulence.

Beyond Word Frequency: Bursts, Lulls, and Scaling in the Temporal Distributions of Words:

Zipf’s discovery that word frequency distributions obey a power law established parallels between biological and physical processes, and language, laying the groundwork for a complex systems perspective on human communication. More recent research has also identified scaling regularities in the dynamics underlying the successive occurrences of events, suggesting the possibility of similar findings for language as well. By considering frequent words in USENET discussion groups and in disparate databases where the language has different levels of formality, here we show that the distributions of distances between successive occurrences of the same word display bursty deviations from a Poisson process and are well characterized by a stretched exponential (Weibull) scaling. The extent of this deviation depends strongly on semantic type – a measure of the logicality of each word – and less strongly on frequency. We develop a generative model of this behavior that fully determines the dynamics of word usage. Recurrence patterns of words are well described by a stretched exponential distribution of recurrence times, an empirical scaling that cannot be anticipated from Zipf’s law. Because the use of words provides a uniquely precise and powerful lens on human thought and activity, our findings also have implications for other overt manifestations of collective human dynamics.